Porphyria cutanea tarda (PCT) is the most common form of porphyria affecting humans. The disorder is often associated with liver iron overload, exposure to liver toxins, such as alcohol, hepatitis C virus, and medicinal estrogens, and with a familial history of the disorder. The genetic defects underlying this disorder are mutations affecting a gene designated the uroporphyrinogen decarboxylase (URO-D) gene. A proportion of patients with PCT have mutations at one allele of URO-D, but most subjects with such mutations do not express signs or symptoms of the disease. Drs. Kushner and Phillips are attempting to determine why the disease is expressed, and they are testing the hypothesis that an inhibitor of URO-D is generated in the liver in individuals genetically predisposed to develop PCT when liver iron overload occurs.